chr7-1744656-C-T

Variant names:

• chr7-1744656-C-T
• rs114295521
• NM_001128636.4:c.60C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001128636.4(ELFN1):​c.60C>T​(p.His20His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,550,412 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: ELFN1 NM_001128636.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400
• Publications: 0 publications found

Genes affected

ELFN1 (HGNC:33154): (extracellular leucine rich repeat and fibronectin type III domain containing 1) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in synapse organization. Predicted to be located in dendrite and excitatory synapse. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-1744656-C-T is Benign according to our data. Variant chr7-1744656-C-T is described in ClinVar as Benign. ClinVar VariationId is 768128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.04 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128636.4. 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
	ELFN1	NM_001128636.4	MANE Select	c.60C>T	p.His20His	synonymous	Exon 4 of 4	NP_001122108.1	P0C7U0
	ELFN1	NM_001394187.1		c.60C>T	p.His20His	synonymous	Exon 3 of 3	NP_001381116.1	P0C7U0
	ELFN1	NM_001394188.1		c.60C>T	p.His20His	synonymous	Exon 4 of 4	NP_001381117.1	P0C7U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELFN1	ENST00000424383.5	TSL:5 MANE Select	c.60C>T	p.His20His	synonymous	Exon 4 of 4	ENSP00000456548.1	P0C7U0
	ELFN1	ENST00000561626.4	TSL:2	c.60C>T	p.His20His	synonymous	Exon 3 of 3	ENSP00000457193.1	P0C7U0
	ELFN1	ENST00000691883.1		c.60C>T	p.His20His	synonymous	Exon 3 of 3	ENSP00000510296.1	P0C7U0

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152102 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000885 AC: 135 AN: 152578 AF XY: 0.000863

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000691

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000186

Gnomad FIN exome AF: 0.000564

Gnomad NFE exome AF: 0.0000172

Gnomad OTH exome AF: 0.000693

GnomAD4 exome AF: 0.000393 AC: 550 AN: 1398192 Hom.: 2 Cov.: 31 AF XY: 0.000352 AC XY: 243 AN XY: 689628

African (AFR) AF: 0.0117 AC: 369 AN: 31578

American (AMR) AF: 0.000953 AC: 34 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25148

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35720

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79184

European-Finnish (FIN) AF: 0.000719 AC: 35 AN: 48670

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.0000593 AC: 64 AN: 1078578

Other (OTH) AF: 0.000742 AC: 43 AN: 57950

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152220 Hom.: 4 Cov.: 33 AF XY: 0.00352 AC XY: 262 AN XY: 74434

African (AFR) AF: 0.0122 AC: 506 AN: 41540

American (AMR) AF: 0.000784 AC: 12 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67984

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.00400

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.5
DANN	Benign	0.88
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs114295521; hg19: chr7-1784292;