19-44708135-T-C

Variant names:

• chr19-44708135-T-C
• rs61744497
• NM_001039213.4:c.1215T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001039213.4(CEACAM16):​c.1215T>C​(p.Thr405Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,606,178 control chromosomes in the GnomAD database, including 591,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (59993 hom., cov: 33)
  • Exomes 𝑓: 0.85 (531874 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.92
• Publications: 16 publications found

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-44708135-T-C is Benign according to our data. Variant chr19-44708135-T-C is described in ClinVar as Benign. ClinVar VariationId is 769228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	NM_001039213.4	MANE Select	c.1215T>C	p.Thr405Thr	synonymous	Exon 6 of 7	NP_001034302.2
	CEACAM16-AS1	NR_186815.1		n.348-8958A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.1215T>C	p.Thr405Thr	synonymous	Exon 6 of 7	ENSP00000466561.1
	CEACAM16	ENST00000405314.2	TSL:5	c.1215T>C	p.Thr405Thr	synonymous	Exon 5 of 6	ENSP00000385576.1
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.314+7815A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134654 AN: 152154 Hom.: 59930 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 0.855 AC: 1242633 AN: 1453906 Hom.: 531874 Cov.: 73 AF XY: 0.855 AC XY: 617749 AN XY: 722278

African (AFR) AF: 0.973 AC: 32433 AN: 33320

American (AMR) AF: 0.952 AC: 41754 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 21779 AN: 25936

East Asian (EAS) AF: 0.782 AC: 30741 AN: 39294

South Asian (SAS) AF: 0.894 AC: 75799 AN: 84760

European-Finnish (FIN) AF: 0.785 AC: 41419 AN: 52770

Middle Eastern (MID) AF: 0.934 AC: 5357 AN: 5738

European-Non Finnish (NFE) AF: 0.849 AC: 941363 AN: 1108140

Other (OTH) AF: 0.865 AC: 51988 AN: 60080

GnomAD4 genome AF: 0.885 AC: 134775 AN: 152272 Hom.: 59993 Cov.: 33 AF XY: 0.883 AC XY: 65718 AN XY: 74446

African (AFR) AF: 0.968 AC: 40228 AN: 41568

American (AMR) AF: 0.930 AC: 14224 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3470

East Asian (EAS) AF: 0.757 AC: 3912 AN: 5168

South Asian (SAS) AF: 0.900 AC: 4353 AN: 4834

European-Finnish (FIN) AF: 0.774 AC: 8208 AN: 10598

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58054 AN: 68014

Other (OTH) AF: 0.894 AC: 1890 AN: 2114

Alfa AF: 0.862 Hom.: 66093

Bravo AF: 0.898

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.12
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs61744497; hg19: chr19-45211407;