NM_000441.2:c.-3-109dupG

Variant names:

• chr7-107661524-A-AG
• rs200483647
• NM_000441.2:c.-3-109dupG

Variant summary

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

The NM_000441.2(SLC26A4):​c.-3-109dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,177,642 control chromosomes in the GnomAD database, including 196 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (26 hom., cov: 32)
  • Exomes 𝑓: 0.017 (170 hom.)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.397
• Publications: 0 publications found

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

ACMG classification

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

• BP6: Variant 7-107661524-A-AG is Benign according to our data. Variant chr7-107661524-A-AG is described in ClinVar as Likely_benign. ClinVar VariationId is 1209241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.015 (2281/152288) while in subpopulation NFE AF = 0.0226 (1534/68008). AF 95% confidence interval is 0.0216. There are 26 homozygotes in GnomAd4. There are 1095 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. 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
	SLC26A4	NM_000441.2	MANE Select	c.-3-109dupG		intron	N/A	NP_000432.1	O43511-1
	SLC26A4-AS1	NR_028137.1		n.197+77dupC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.-3-109dupG		intron	N/A	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.-112dupG		5_prime_UTR	Exon 1 of 20	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.-3-109dupG		intron	N/A	ENSP00000558759.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2281 AN: 152170 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00400

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0172 AC: 17609 AN: 1025354 Hom.: 170 Cov.: 14 AF XY: 0.0167 AC XY: 8641 AN XY: 518600

African (AFR) AF: 0.00295 AC: 73 AN: 24786

American (AMR) AF: 0.0102 AC: 355 AN: 34866

Ashkenazi Jewish (ASJ) AF: 0.0241 AC: 537 AN: 22252

East Asian (EAS) AF: 0.0000294 AC: 1 AN: 33980

South Asian (SAS) AF: 0.00332 AC: 232 AN: 69784

European-Finnish (FIN) AF: 0.0201 AC: 671 AN: 33432

Middle Eastern (MID) AF: 0.00140 AC: 5 AN: 3576

European-Non Finnish (NFE) AF: 0.0199 AC: 15102 AN: 757036

Other (OTH) AF: 0.0139 AC: 633 AN: 45642

GnomAD4 genome AF: 0.0150 AC: 2281 AN: 152288 Hom.: 26 Cov.: 32 AF XY: 0.0147 AC XY: 1095 AN XY: 74468

African (AFR) AF: 0.00399 AC: 166 AN: 41572

American (AMR) AF: 0.0135 AC: 207 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4828

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0226 AC: 1534 AN: 68008

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0112 Hom.: 6

Bravo AF: 0.0131

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 provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
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: rs200483647; hg19: chr7-107301969;