7-103542700-GT-GTT

Variant names:

• chr7-103542700-G-GT
• rs150971291
• NM_005045.4:c.6671+30dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005045.4(RELN):​c.6671+30dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 1,611,704 control chromosomes in the GnomAD database, including 71 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (67 hom.)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214
• Publications: 0 publications found

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

RELN Gene-Disease associations (from GenCC):

• lissencephaly with cerebellar hypoplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Norman-Roberts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
• familial temporal lobe epilepsy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-103542700-G-GT is Benign according to our data. Variant chr7-103542700-G-GT is described in ClinVar as Likely_benign. ClinVar VariationId is 259611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00544 (828/152178) while in subpopulation NFE AF = 0.00832 (566/67996). AF 95% confidence interval is 0.00776. There are 4 homozygotes in GnomAd4. There are 388 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005045.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	NM_005045.4	MANE Select	c.6671+30dupA		intron	N/A	NP_005036.2
	RELN	NM_173054.3		c.6671+30dupA		intron	N/A	NP_774959.1	P78509-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELN	ENST00000428762.6	TSL:5 MANE Select	c.6671+30_6671+31insA		intron	N/A	ENSP00000392423.1	P78509-1
	RELN	ENST00000424685.3	TSL:5	c.6671+30_6671+31insA		intron	N/A	ENSP00000388446.3	J3KQ66
	RELN	ENST00000343529.9	TSL:5	c.6671+30_6671+31insA		intron	N/A	ENSP00000345694.5	P78509-2

Frequencies

GnomAD3 genomes AF: 0.00544 AC: 827 AN: 152060 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00584 AC: 1465 AN: 251014 AF XY: 0.00591

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00366

Gnomad NFE exome AF: 0.00929

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00841 AC: 12275 AN: 1459526 Hom.: 67 Cov.: 31 AF XY: 0.00833 AC XY: 6048 AN XY: 726198

African (AFR) AF: 0.00111 AC: 37 AN: 33412

American (AMR) AF: 0.00230 AC: 103 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00280 AC: 73 AN: 26066

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39600

South Asian (SAS) AF: 0.00576 AC: 497 AN: 86224

European-Finnish (FIN) AF: 0.00491 AC: 262 AN: 53320

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5764

European-Non Finnish (NFE) AF: 0.00971 AC: 10778 AN: 1110166

Other (OTH) AF: 0.00811 AC: 489 AN: 60272

GnomAD4 genome AF: 0.00544 AC: 828 AN: 152178 Hom.: 4 Cov.: 32 AF XY: 0.00522 AC XY: 388 AN XY: 74390

African (AFR) AF: 0.00185 AC: 77 AN: 41526

American (AMR) AF: 0.00726 AC: 111 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4820

European-Finnish (FIN) AF: 0.00293 AC: 31 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00832 AC: 566 AN: 67996

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00263 Hom.: 0

Bravo AF: 0.00597

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150971291; hg19: chr7-103183147;